rs481809

Variant names:

• chr3-101293262-C-G
• rs481809
• NM_016247.4:c.502-1752G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016247.4(IMPG2):​c.502-1752G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,072 control chromosomes in the GnomAD database, including 40,380 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (40380 hom., cov: 31)
• Consequence: IMPG2 NM_016247.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473
• Publications: 0 publications found

Genes affected

IMPG2 (HGNC:18362): (interphotoreceptor matrix proteoglycan 2) The protein encoded by this gene binds chondroitin sulfate and hyaluronan and is a proteoglycan. The encoded protein plays a role in the organization of the interphotoreceptor matrix and may promote the growth and maintenance of the light-sensitive photoreceptor outer segment. Defects in this gene are a cause of retinitis pigmentosa type 56 and maculopathy, IMPG2-related.[provided by RefSeq, Mar 2011]

IMPG2 Gene-Disease associations (from GenCC):

• vitelliform macular dystrophy 5

  Inheritance: AD, Unknown Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• IMPG2-related recessive retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 56

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• adult-onset foveomacular vitelliform dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016247.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPG2	NM_016247.4	MANE Select	c.502-1752G>C		intron	N/A	NP_057331.2	Q9BZV3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPG2	ENST00000193391.8	TSL:1 MANE Select	c.502-1752G>C		intron	N/A	ENSP00000193391.6	Q9BZV3

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109152 AN: 151954 Hom.: 40349 Cov.: 31

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.706

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.718 AC: 109215 AN: 152072 Hom.: 40380 Cov.: 31 AF XY: 0.724 AC XY: 53850 AN XY: 74334

African (AFR) AF: 0.528 AC: 21920 AN: 41476

American (AMR) AF: 0.784 AC: 11984 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2586 AN: 3472

East Asian (EAS) AF: 0.837 AC: 4314 AN: 5156

South Asian (SAS) AF: 0.784 AC: 3771 AN: 4812

European-Finnish (FIN) AF: 0.849 AC: 8979 AN: 10578

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53420 AN: 67978

Other (OTH) AF: 0.708 AC: 1492 AN: 2106

Alfa AF: 0.748 Hom.: 5437

Bravo AF: 0.705

Asia WGS AF: 0.774 AC: 2692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.83
DANN	Benign	0.57
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs481809; hg19: chr3-101012106;